Inhibition of nuclear factor kappaB activation by a virus-encoded IkappaB-like protein.
Certain viruses have evolved mechanisms to counteract innate immunity, a host response in which nuclear factor kappaB (NF-kappaB) transcription factors play a central role. African swine fever virus encodes a protein of 28.2 kDa containing ankyrin repeats similar to those of cellular IkappaB proteins, which are inhibitors of NF-kappaB. Transfection of the African swine fever virus IkappaB gene inhibited tumor necrosis factor- or phorbol ester-induced activation of kappaB- but not AP-1-driven reporter genes. Moreover, African swine fever virus IkappaB co-immunoprecipitated with p65 NF-kappaB, and the purified recombinant protein prevented the binding of p65-p50 NF-kappaB proteins to their target sequences in the DNA. NF-kappaB activation induced by tumor necrosis factor, as detected by mobility shift assays or by transfection of kappaB-driven reporter genes, is impaired in African swine fever virus-infected cells. These results indicate that the African swine fever virus IkappaB gene homologue interferes with NF-kappaB activation, likely representing a new mechanism to evade the immune response during viral infection.
Revilla
Y
Y
Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain.
Callejo
M
M
Rodríguez
J M
JM
Culebras
E
E
Nogal
M L
ML
Salas
M L
ML
Viñuela
E
E
Fresno
M
M
D000358:African Swine Fever Virus / Q000235:genetics* / Q000254:growth & development; D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005814:Genes, Viral; D020672:I-kappa B Proteins; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells / Q000821:virology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D014764:Viral Proteins; D000072000:NF-KappaB Inhibitor alpha